The effects of adriamycin analogs on cardiotoxicity was studied in cultured cardiomyocytes. The earliest structural effects observed in the cardiomyocytes were vacuolization and nuclear fragmentation at 4 hrs. after treatment with adriamycin (ADR) (100 ug/ml). While daunomycin (DAUN) analog of adriamycin, containing a methyl group in place of hydroxymethyl group showed much more drastic effects at lower concentration, DAUN caused an immediate cessation of beating of cells along with changes in the cell shape as well as lifting of cells from the plate. Cytoplasmic enzyme leakage into the medium was used as an index of cell toxicity induced by ADR and DAUN. Quantitative measurement of LDH leakage indicated that DAUN was 3-4 times more toxic in causing cell death than adriamycin. Measurement of malanaldehyde release indicated that adriamycin toxicity may not be related to lipid peroxidation